Cross-sensitization between footshock stress and apomorphine on self-injurious behavior and neostriatal catecholamines in a rat model of Lesch-Nyhan syndrome.
The effects of footshock sensitization (priming), apomorphine (APO) priming and their combination on behavior and neostriatal and cortical catecholamines were examined in adult rats which had neonatally received bilateral intracerebroventricular injections with 6-hydroxydopamine (6-OHDA; a model of Lesch-Nyhan syndrome (LNS)) or vehicle (unlesioned rats). Lesioned (6-OHDA-treated) rats displayed self-biting (SB; 7/20 rats) and self-injurious behavior (SIB; 1/20 rats) during APO priming, but not during footshock priming. During subsequent acute cumulative APO dosing, 20-30% of lesioned rats primed with APO alone or footshock alone displayed SB and SIB. However, SB and SIB incidence in APO+footshock-primed lesioned rats was nearly tripled. Dopamine (DA) synthesis, metabolism and extracellular concentrations (disposition) in unlesioned rats and in cortices of lesioned animals were unaffected by priming. In lesioned rats primed with APO alone or footshock alone, only neostriatal 3-methoxytyramine (3-MT) was significantly increased. However, neostriatal DA and metabolite concentrations (and norepinephrine (NE)) were all significantly elevated in lesioned rats primed with both APO and footshock. These results confirm that neonatal 6-OHDA-induced neostriatal catecholamine depletion can be antagonized by experiential change, suggest that behavioral and neurochemical cross-sensitization between APO and footshock in such rats is unidirectional and support the view that stress can exacerbate the incidence of SIB in LNS.
Stodgell
C J
CJ
Department of Pharmacology and Toxicology, 5036A Malott, School of Pharmacy, University of Kansas, Lawrence, KS 66045-2505, USA.
Loupe
P S
PS
Schroeder
S R
SR
Tessel
R E
RE
D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D004597:Electroshock; D007276:Injections, Intraventricular; D007926:Lesch-Nyhan Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D016728:Self-Injurious Behavior; D013312:Stress, Physiological / Q000378:metabolism / Q000523:psychology*
D002395:Catecholamines; D018491:Dopamine Agonists; D009498:Neurotoxins; D016627:Oxidopamine; D001058:Apomorphine